Neuritic plaque amyloid is the pathological finding that defines Alzheimer's disease. Amyloid deposition accompanies a large number of other diseases and is often responsible for their morbidity and lethality. Amyloid has been found in all cases to be primarily proteinaceous in composition. The amyloid that accompanies each disease is composed of one major protein characteristic of that disease. Amyloid may result from either over-production or impaired degradation of a normal serum protein. From these observations we hypothesize that Alzheimer neuritic plaque amyloid likewise results from the aberrant metabolism of a serum protein, and that this process is directly related to the causes and consequences of the disease. We are testing this hypothesis by isolating the various forms of Alzheimer amyloid, characterizing them via peptide sequencing, and identifying and isolating the amyloid precursor. We will identify the process that converts the precursor to the amyloid peptide by characterizing these proteins' structural differences. We will search for differences between the normal precursor and the precursor in Alzheimer serum that might account for its deposition as amyloid. Such differences might include amino acid sequence variations or alterations in post translational modifications. Differences in phosphorylation, glycosylation or methylation initially may be revealed in peptide maps. If the precursors prove to be identical in structure and amount, we would conclude that amyloid deposition results from abnormal catabolism of the precursor.